Topical potent corticosteroids are the mainstay of treatment for chronic hand eczema (CHE). However, there are numerous adverse effects associated with the chronic use of topical corticosteroids. Calcipotriol has been widely used in psoriasis and has been reported to achieve beneficial effects in several inflammatory diseases. This study aimed to evaluate the efficacy and safety of calcipotriol ointment compared to desoximetasone ointment in the treatment of CHE. Patch testing was performed in all recruited subjects. Then, each hand of the patient was randomly allocated for the application of either calcipotriol ointment or desoximetasone ointment twice daily for 8 weeks. Recurrence was assessed 4 weeks after discontinuation of the treatment. The Hand eczema severity index (HECSI) scores, quartile grading assessments and digital photographs were evaluated. Adverse reactions were also monitored. A total of 13 participants completed the protocol. Mean HECSI scores revealed up to a 75% reduction in both treatments (p < .001) without significant differences between the groups (p > .05). Approximately 70% of the subjects reported more than 75% improvement with calcipotriol at the end of the treatment. Mild scaling and mild dryness were the most common reactions found with calcipotriol and desoximetasone, respectively. In conclusion, calcipotriol ointment is safe and as effective as desoximetasone ointment. Calcipotriol ointment may be an alternative treatment option for CHE.